ROLE OF EPIGENETIC MODIFICATIONS IN TUMOR SUPPRESSOR GENE SILENCING AMONG PATIENTS WITH SPORADIC COLORECTAL CANCER: NARRATIVE REVIEW

Background: Sporadic colorectal cancer (CRC), which constitutes the majority of CRC cases, is primarily driven by acquired molecular changes rather than inherited mutations. Among these, epigenetic alterations—specifically the silencing of tumor suppressor genes—play a crucial role in colorectal tumorigenesis. Understanding these reversible and dynamic modifications offers significant potential for enhancing early detection, prognosis, and targeted therapy. Objective: This narrative review aims to explore the role of epigenetic modifications in the silencing of tumor suppressor genes in patients with sporadic colorectal cancer, synthesizing current findings and identifying implications for clinical practice and future research. Main Discussion Points: Key epigenetic mechanisms discussed include promoter hypermethylation of genes such as MLH1, MGMT, and CDKN2A; long-range epigenetic silencing across chromosomal regions; histone modification patterns contributing to chromatin inactivation; and microRNA suppression involved in early tumorigenesis. The review also highlights variability in study methodologies, population-specific differences, and gaps in longitudinal and functional research. Limitations related to sample size, design, and generalizability are critically analyzed. Conclusion: Epigenetic silencing of tumor suppressor genes is a central event in sporadic CRC development, with clear implications for biomarker discovery and therapeutic targeting. While current evidence is promising, more standardized and mechanistically focused studies are needed to translate these findings into clinical applications and guidelines.